1. Field of the Invention
This invention relates generally to the field of medicine. In particular, it relates to methods and compositions that are especially suitable for the treatment of hyperhidrosis, and other conditions of the glands, skin, or smooth and skeletal muscle, and involve the topical application of one or more microbial neurotoxins.
2. Description of the Related Art
Traditionally, bacterial toxins, such as those produced by the genus Clostridia, were best known for their wide-ranging pathogenic effects, including food poisoning, tetanus, and botulism. Virulent botulinum strains are divided into seven groups, with each group producing an antigenically distinct toxin (the so-called types A-G toxins). While the potency of these toxins differ somewhat (and their physiological modes of action vary), they all result in chemodenervation.
Remarkably, the toxins produced by Clostridium botulinum are one of the few large molecules that are absorbed intact from the gastrointestinal tract, where they enter the bloodstream and prevent the contraction of skeletal muscles primarily by inhibiting the release of acetylcholine from nerve cells. One of the more gruesome conditions caused by the ingestion of C. botulinum toxin, botulism is a rare but often fatal disease. Symptoms of botulism can include blurred vision, nausea and vomiting, and progressive weakness. Death often results from a gradual paralysis of the muscles required for respiration.
Ironically, it is this “paralytic” property that has led to the development of therapeutic uses for botulinum toxin beginning in the 1960's. In fact, botulinum toxin is now safely used in the treatment of over a dozen human diseases involving hyperactive skeletal muscles. More generally, pharmaceutical preparations of botulinum toxin are used for the treatment of neurological disorders, muscle dystonias, smooth muscle disorders, autonomic nerve disorders, headaches, wrinkles, sports injuries, cerebral palsy, spasms, tremors and pain.
Much recent research has focused on the use of botulinum A toxin to block the release of acetylcholine from autonomic nerve endings which control glandular tissue and smooth muscle. This effort has mainly focused on using the toxin to treat hyperhidrosis (excessive sweating) in the axillae and palmar hands. Hyperhidrosis of the palms, soles of the feet, and axillae is caused by excessive episodic sweating from the eccrine glands (as well as the apocrine glands in the axilla). This disorder, which appears to be genetically based, is a cause of great distress for sufferers. It can also be expensive. Aside from the disruption of normal social activities, excessive sweating frequently discolors and thereby ruins clothing.
Traditional therapies for hyperhidrosis include the use of topical aluminum chloride salts such as found in antiperspirants, glutaraldehyde mixtures, anticholinergic drugs, direct excision of affected skin, liposuction and thoracic sympathectomies. All of these therapies have significant drawbacks and are often unsuccessful. Thus, the use of botulinum toxins for chemodenervation for hyperhidrosis has gained in popularity over the last several years.
Presently, hyperhidrosis is treated with botulinum A, which is commercially produced under the trademark “BOTOX.” In a typical treatment regime, BOTOX is injected intradermally in the axilla, palms, and soles with a significant, albeit temporary, effect on reducing sweating. However, intradermal injection-based treatments for hyperhidrosis also have several significant drawbacks.
First, introducing BOTOX through intradermal injections is painful and often involves numerous percutaneous sticks in order to provide relief for the affected area. Moreover, because relief is only temporary, having a medical practioner administer each follow-up injection can be time-consuming, costly, and inconvenient.
Based on these drawbacks for existing treatment options, there remains a need in the art for an effective, long-lasting, and painless treatment for glandular disorders such as hyperhidrosis.